Involvement of CRH-R2 receptor in eating behavior and in the response of the HPT axis in rats subjected to dehydration-induced anorexia.
Wistar rats subjected to dehydration-induced anorexia (DIA), with 2.5% NaCl solution as drinking water for 7 days, decrease by 80% their food intake and present some changes common to pair-fed food restricted rats (FFR) such as: weight loss, decreased serum leptin and expression of orexigenic arcuate peptides, increasing the anorexigenic ones and serum corticosterone levels. In contrast, the response of the HPT axis differs: DIA animals have increased TRH expression in PVN and present primary as opposed to the tertiary hypothyroidism of the FFR. Exclusive to DIA is the activation of CRHergic neurons in the lateral hypothalamus (LH) that project to PVN. Since TRH neurons of the PVN contain CRH receptors, we hypothesized that the differences in the response of the HPT axis to DIA could be due to CRH regulating TRHergic neurons. CRH effect was first evaluated on TRH expression of cultured hypothalamic cells where TRH mRNA levels increased after 1h with 0.1nM of CRH. We then measured the mRNA levels of CRH receptors in the PVN of male and female rats subjected to DIA; only those of CRH-R2 were modulated (down-regulated). The CRH-R2 antagonist antisauvagine-30 was therefore injected into the PVN of male rats, during the 7 days of DIA. Antisauvagine-30 induced a higher food intake than controls, and impeded the changes produced by DIA on the HPT axis: PVN TRH mRNA, and serum TH and TSH levels were decreased to similar values of FFR animals. Results corroborate the anorexigenic effect of CRH and show its role, acting through CRH-R2 receptors, in the activation of TRHergic PVN neurons caused by DIA. These new data further supports clinical trials with CRH-R2 antagonists in anorexia nervosa patients.
de Gortari
Patricia
P
División de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría RFM, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México, D.F., Mexico; Escuela de Dietética y Nutrición del ISSSTE, Callejón Vía San Fernando 12, Col. San Pedro Apóstol, 14070 México, D.F., Mexico. Electronic address: gortari@imp.edu.mx.
Mancera
Karen
K
División de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría RFM, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México, D.F., Mexico.
Cote-Vélez
Antonieta
A
Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), A.P. 510-3, Mor 62210, Mexico.
Amaya
María Isabel
MI
División de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría RFM, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México, D.F., Mexico.
Martínez
Adrián
A
División de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría RFM, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México, D.F., Mexico.
Jaimes-Hoy
Lorraine
L
División de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría RFM, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México, D.F., Mexico; Escuela de Dietética y Nutrición del ISSSTE, Callejón Vía San Fernando 12, Col. San Pedro Apóstol, 14070 México, D.F., Mexico.
Joseph-Bravo
Patricia
P
Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), A.P. 510-3, Mor 62210, Mexico.
D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000378:metabolism*; D002478:Cells, Cultured; D003681:Dehydration / Q000150:complications; D015536:Down-Regulation; D005247:Feeding Behavior; D005260:Female; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010902:Pituitary Gland / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012727:Sex Characteristics; D013961:Thyroid Gland / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism
C101531:CRF receptor type 2; D010446:Peptide Fragments; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C116607:antisauvagine 30; D013973:Thyrotropin-Releasing Hormone